聚乙二醇干扰素 λ 早期治疗 COVID-19。
Early Treatment with Pegylated Interferon Lambda for Covid-19.
机构信息
From ViRx@Stanford, Stanford Biosecurity and Pandemic Preparedness Initiative (G.R., J.S.G., E.J.M.), and the Departments of Medicine (Division of Gastroenterology and Hepatology) and Microbiology and Immunology, Stanford University School of Medicine (J.S.G.), Stanford, and the Veterans Affairs Medical Center (J.S.G.) and Eiger BioPharmaceuticals (C.H., I.C.), Palo Alto - all in California; the Research Division, Cardresearch-Cardiologia Assistencial e de Pesquisa (G.R., E.A.S.M.S., D.C.M.S., V.H.S.C., T.S.F., C.V.Q.S., M.I.C.S., L.B.R., R.O.), the Department of Medicine, Pontifícia Universidade Católica de Minas Gerais (G.R., E.A.S.M.S., D.C.M.S., V.H.S.C., C.V.Q.S.), and Target Medicina de Precisão (A.C.F.D., A.M.F.J.), Belo Horizonte, the Department of Public Health and Mental and Family Medicine, Ouro Preto Federal University, Ouro Preto (L.C.M.S., C.B., A.C.M.), the Public Health Care Division, Ibirité (C.B., A.C.M.), the Department of Public Health at UNIFIPMoc and Family Medicine Fellowship Program, Montes Claros (A.M.R.N., A.P.F.G.A.), the Public Health Fellowship Program, Governador Valadares Public Health Authority, Governador Valadares (A.D.F.-N.), and the Public Health Care Division, Brumadinho (E.D.C., B.H.) - all in Brazil; the Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON (G.R., L.T., S.S., P.M., G.H.G., E.J.M.), Cytel (O.H., H.R., P.A., E.J.M.), Platform Life Sciences (L.A.W., J.I.F., C.M.G., E.J.M.), and RainCity Analytics (E.H.L.-O., S.K.), Vancouver, BC, Michael Garron Hospital (C.K.) and the Toronto Centre for Liver Disease, University Health Network (M.A.Z., J.J.F.), University of Toronto, the School of Nursing, York University (M.J.B.), and Sunnybrook Health Sciences Centre (R.K.), Toronto - all in Canada; Certara, Princeton, NJ (C.R.R.); Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia (C.R.R.); and Erasmus University Rotterdam, Rotterdam, the Netherlands (B.H.).
出版信息
N Engl J Med. 2023 Feb 9;388(6):518-528. doi: 10.1056/NEJMoa2209760.
BACKGROUND
The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear.
METHODS
We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization.
RESULTS
A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups.
CONCLUSIONS
Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).
背景
对于急性有症状的 2019 年冠状病毒病（COVID-19）门诊患者，单次使用聚乙二醇干扰素 lambda 的疗效预防临床事件尚不清楚。
方法
我们在巴西和加拿大进行了一项随机、对照、适应性平台试验，该试验主要纳入了严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的接种过疫苗的成年人。在症状出现后 7 天内出现符合 COVID-19 的急性临床症状的门诊患者，接受聚乙二醇干扰素 lambda（单次皮下注射，180μg）或安慰剂（单次注射或口服）治疗。主要复合结局是随机分组后 28 天内因 COVID-19 住院（或转至三级医院）或因 COVID-19 到急诊就诊（观察>6 小时）。
结果
共有 933 名患者被分配接受聚乙二醇干扰素 lambda 治疗（2 名因违反方案被排除），1018 名患者被分配接受安慰剂治疗。总体而言，83%的患者已接种疫苗，在试验过程中，出现了多种 SARS-CoV-2 变体。干扰素组的 931 名患者中有 25 名（2.7%）发生主要结局事件，安慰剂组的 1018 名患者中有 57 名（5.6%），差异为 51%（相对风险，0.49；95%贝叶斯可信区间，0.30 至 0.76；安慰剂优势的后验概率，>99.9%）。次要结局分析结果基本一致，包括 COVID-19 住院时间（风险比，0.57；95%贝叶斯可信区间，0.33 至 0.95）和 COVID-19 相关住院或死亡（风险比，0.59；95%贝叶斯可信区间，0.35 至 0.97）。这些影响在主要变体中是一致的，且独立于疫苗接种状态。在基线病毒载量较高的患者中，接受聚乙二醇干扰素 lambda 治疗的患者在第 7 天的病毒载量低于接受安慰剂治疗的患者。两组不良反应发生率相似。
结论
在 COVID-19 接种过疫苗的门诊患者中，与安慰剂相比，单次使用聚乙二醇干扰素 lambda 治疗可显著降低住院或到急诊就诊（观察>6 小时）的发生率。（由 FastGrants 等资助；TOGETHER 临床试验。gov 编号，NCT04727424。）
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